Despite the dramatic advances in prevention, diagnosis, and treatment made during the last half of the 20th century cardiovascular disease remains the number-one cause of morbidity and death in the United States. The success of angioplasty, vascular surgery procedures, and even heart transplantation (all approaches to treat vaso-occlusive disease) is limited by intimal hyperplasia. The success of angioplasty, vascular surgery procedures, and even heart transplantation (all approaches to treat vaso-occlusive constant infusions of inotropes or with left ventricular assist devices. However, in many instances these treatments only transiently postpone the inevitable death or transplantation. Clearly more effective and sustainable therapies are needed. Gene therapy offers perhaps the greatest opportunity to make the next major advance in preventing or treating cardiovascular disease. While pharmacologic methods typically require frequent closing, a single gene therapy application may be adequate to prevent, attenuate, or reverse even chronic disease. including useful vectors, methods of delivery and the molecular basis of many cardiovascular diseases in humans is the natural progression of ongoing research in cardiovascular gene therapy at the University of Pittsburgh. Two independent research programs, one aimed at developing gene therapy approaches to treat heart failure and the investigators in the Pittsburgh Human Gene Therapy Center (PHGTC). We now propose to further link these established research programs with the extensive resources of the PHGTC and other key resources in the Cores cardiovascular therapy programs from the bench to the bedside. Second, through our proposed preclinical projects, we will acquire the essential data needed to determine if other promising genes, gene targets and vectors projects, we will develop more effective vectors to target cardiovascular tissues. Fourth, through an organized and comprehensive training program, we will prepare clinician scientists for careers in gene therapy for cardiovascular disease. Fifth, through our coordinating data management core, we will provide communication mechanisms and data organization for our consortium centers.